MUS81 Inhibition Increases the Sensitivity to Therapy Effect in Epithelial Ovarian Cancer via Regulating CyclinB Pathway

: MUS81 is a key endonuclease involved in homologous recombination (HR) repair after DNA double-strand damage. Structure-specific endonucleases (SSEs) plays a crucial role in DNA replication, repair and transcription, and SSEs are also important for maintaining the secondary structure of DNA; therefore, their activity must be precisely controlled to ensure genome stability. We previously described that MUS81 expression was significantly correlated with CyclinB expression based on protein microarray analysis. CyclinB is a cell-cycle regulatory protein that has been shown to be involved in the activation of DNA damage repair checkpoints by inducing G2/M phase arrest, promoting apoptosis, and participating in the regulation of chemotherapeutic drug sensitivity by inducing nuclear degradation, as shown by immunofluorescence assays. In this study, MUS81-downregulated cells were generated using lentivirus-mediated RNAi. Our results demonstrated that the inhibition of MUS81 expression activated the CHK1 and CyclinB signaling pathways and sensitized ovarian cancer cells to X-ray and Olaparib treatment both in vitro and in vivo. MUS81 may be a potential therapeutic target for epithelial ovarian cancer (EOC).